-
Journal of Investigational Allergology... 2011There are no previous Spanish guidelines or consensus statements on bradykinin-induced angioedema. (Review)
Review
BACKGROUND
There are no previous Spanish guidelines or consensus statements on bradykinin-induced angioedema.
AIM
To draft a consensus statement on the management and treatment of angioedema mediated by bradykinin in light of currently available scientific evidence and the experience of experts. This statement will serve as a guideline to health professionals.
METHODS
The consensus was led by the Spanish Study Group on Bradykinin-Induced Angioedema, a working group of the Spanish Society of Allergology and Clinical Immunology. A review was conducted of scientific papers on different types of bradykinin-induced angioedema (hereditary and acquired angioedema due to C1 inhibitor deficiency, hereditary angioedema related to estrogens, angioedema induced by angiotensin-converting enzyme inhibitors). Several discussion meetings were held to reach the consensus.
RESULTS
Treatment approaches are discussed, and the consensus reached is described. Specific situations are addressed, namely, pregnancy, contraception, travelling, blood donation, and organ transplantation.
CONCLUSIONS
A review of and consensus on treatment of bradykinin-induced angioedema is presented.
Topics: Angioedema; Bradykinin; Humans; Prognosis
PubMed: 21995176
DOI: No ID Found -
The Journal of Biological Chemistry Jul 1984We employed des-Arg9-bradykinin to investigate the relation between bradykinin-induced prostaglandin (PG) synthesis and bradykinin-induced protein accumulation. In this...
We employed des-Arg9-bradykinin to investigate the relation between bradykinin-induced prostaglandin (PG) synthesis and bradykinin-induced protein accumulation. In this feedback control system, bradykinin-induced PG synthesis limits bradykinin-induced protein production. At low concentration (5 X 10(-8) M), des-Arg9-bradykinin was significantly less active than bradykinin in stimulating the formation of prostaglandins by human fetal lung fibroblasts in culture. At high concentration (5 X 10(-6) M), bradykinin induced a 24% increase in protein formation, while des-Arg9-bradykinin induced a 61% increase in collagen formation and an 80% increase in total protein accumulation. In the presence of indomethacin, bradykinin-induced protein formation was increased further, whereas des-Arg9-bradykinin-induced protein formation was unchanged. The bradykinin derivative increased the production of types I and III procollagens without affecting the distribution of procollagen types. The incorporation of [3H]thymidine into DNA in lung fibroblast cultures was increased 3-fold by des-Arg9-bradykinin alone or by bradykinin in combination with indomethacin. Des-Arg9-[Leu8]bradykinin inhibited the des-Arg9-bradykinin-induced protein formation and cell division. These data indicate that both bradykinin and des-Arg9-bradykinin stimulate protein formation and cell division; des-Arg9-bradykinin alone stimulates protein formation and cell division without activating PG synthesis and PG feedback control.
Topics: Arachidonic Acid; Arachidonic Acids; Bradykinin; Cell Division; Cell Line; Collagen; DNA Replication; Embryo, Mammalian; Feedback; Fibroblasts; Humans; Indomethacin; Lung; Prostaglandins; Protein Biosynthesis
PubMed: 6430899
DOI: No ID Found -
The American Journal of Managed Care Aug 2018Hereditary angioedema (HAE) is a rare genetic disease defined by recurrent attacks of edema, causing a substantial burden for patients, with morbidity, mortality, and... (Review)
Review
Hereditary angioedema (HAE) is a rare genetic disease defined by recurrent attacks of edema, causing a substantial burden for patients, with morbidity, mortality, and reduced quality of life. This burden is increased by delayed diagnosis, inappropriate treatment, and suboptimal follow-up and patient education. Several novel therapeutics have recently been approved or are currently under evaluation for prevention of HAE attacks.
Topics: Angioedemas, Hereditary; Bradykinin; Bradykinin B2 Receptor Antagonists; Complement C1 Inhibitor Protein; Humans; Kallikreins; Peptides; Recombinant Proteins
PubMed: 30132644
DOI: No ID Found -
International Journal of Molecular... Feb 2024The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the coagulation system is not fully understood. SARS-CoV-2 penetrates cells through... (Observational Study)
Observational Study
The Role of the Kinin System and the Effect of Des-Arginine-Bradykinin on Coagulation and Platelet Function in Critically Ill COVID-19 Patients: A Secondary Analysis of a Prospective Observational Study.
The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the coagulation system is not fully understood. SARS-CoV-2 penetrates cells through angiotensin-converting enzyme 2 (ACE2) receptors, leading to its downregulation. Des-arginine-bradykinin (DA9B) is degraded by ACE2 and causes vasodilation and increased vascular permeability. Furthermore, DA9B is associated with impaired platelet function. Therefore, the aim of this study was to evaluate the effects of DA9B on platelet function and coagulopathy in critically ill coronavirus disease 2019 (COVID-19) patients. In total, 29 polymerase-positive SARS-CoV-2 patients admitted to the intensive care unit of the University Hospital of Giessen and 29 healthy controls were included. Blood samples were taken, and platelet impedance aggregometry and rotational thromboelastometry were performed. Enzyme-linked immunosorbent assays measured the concentrations of DA9B, bradykinin, and angiotensin 2. Significantly increased concentrations of DA9B and angiotensin 2 were found in the COVID-19 patients. A negative effect of DA9B on platelet function and intrinsic coagulation was also found. A sub-analysis of moderate and severe acute respiratory distress syndrome patients revealed a negative association between DA9B and platelet counts and fibrinogen levels. DA9B provokes inhibitory effects on the intrinsic coagulation system in COVID-19 patients. This negative feedback seems reasonable as bradykinin, which is transformed to DA9B, is released after contact activation. Nevertheless, further studies are needed to confirm our findings.
Topics: Humans; COVID-19; SARS-CoV-2; Bradykinin; Angiotensin-Converting Enzyme 2; Critical Illness; Angiotensins
PubMed: 38397016
DOI: 10.3390/ijms25042342 -
Biochimica Et Biophysica Acta.... Oct 2017In recent years a wide range of studies have shown that G protein-coupled receptors modulate a variety of cell functions through the formation of dimers. For instance,...
In recent years a wide range of studies have shown that G protein-coupled receptors modulate a variety of cell functions through the formation of dimers. For instance, there is growing evidence for the dimerization of bradykinin or dopamine receptors, both as homodimers and heterodimers. A discovery of direct interactions of angiotensin II receptors with bradykinin 2 receptor (B2R) or dopamine D2 (D2R) receptor has led to a hypothesis on a potential dimerization between two latter receptors. In this study, we have demonstrated a constitutive colocalization of receptors on the membranes of HEK293 cells transiently transfected with plasmid vectors encoding B2R and D2R, fused with fluorescent proteins. The receptor colocalization was significantly enhanced by specific agonists of B2R or D2R after 5min following the addition, whereas simultaneous stimulation with these agonists did not influence the B2R/D2R colocalization level. In addition, B2R-D2R heterodimerization was confirmed with FLIM-FRET technique. The most characteristic signaling pathways for B2R and D2R, dependent on intracellular Ca and cAMP concentration, respectively, were analyzed in cells presenting similar endogenous expression of B2R and D2R. Significant changes in receptors' signaling were observed after simultaneous stimulation with agonists, suggesting transformations in proteins' conformation after dimerization. The evidence of B2R-D2R dimerization may open new perspectives in the modulation of diverse cellular functions which depend on their activation.
Topics: Bradykinin; Dimerization; HEK293 Cells; Humans; Protein Conformation; Receptor, Bradykinin B2; Receptors, Dopamine D2; Signal Transduction
PubMed: 28757212
DOI: 10.1016/j.bbamcr.2017.07.012 -
Brazilian Journal of Medical and... Jun 2000The kallikrein-kinin system is complex, with several bioactive peptides that are formed in many different compartments. Kinin peptides are implicated in many... (Review)
Review
The kallikrein-kinin system is complex, with several bioactive peptides that are formed in many different compartments. Kinin peptides are implicated in many physiological and pathological processes including the regulation of blood pressure and sodium homeostasis, inflammatory processes, and the cardioprotective effects of preconditioning. We established a methodology for the measurement of individual kinin peptides in order to study the function of the kallikrein-kinin system. The levels of kinin peptides in tissues were higher than in blood, confirming the primary tissue localization of the kallikrein-kinin system. Moreover, the separate measurement of bradykinin and kallidin peptides in man demonstrated the differential regulation of the plasma and tissue kallikrein-kinin systems, respectively. Kinin peptide levels were increased in the heart of rats with myocardial infarction, in tissues of diabetic and spontaneously hypertensive rats, and in urine of patients with interstitial cystitis, suggesting a role for kinin peptides in the pathogenesis of these conditions. By contrast, blood levels of kallidin, but not bradykinin, peptides were suppressed in patients with severe cardiac failure, suggesting that the activity of the tissue kallikrein-kinin system may be suppressed in this condition. Both angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) inhibitors increased bradykinin peptide levels. ACE and NEP inhibitors had different effects on kinin peptide levels in blood, urine, and tissues, which may be accounted for by the differential contributions of ACE and NEP to kinin peptide metabolism in the multiple compartments in which kinin peptide generation occurs. Measurement of the levels of individual kinin peptides has given important information about the operation of the kallikrein-kinin system and its role in physiology and disease states.
Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Bradykinin; Dogs; Feedback; Humans; Kallidin; Kallikrein-Kinin System; Kallikreins; Kinins; Male; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System
PubMed: 10829095
DOI: 10.1590/s0100-879x2000000600008 -
Journal of the... Mar 2000
Review
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Bradykinin; Humans; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2
PubMed: 11967793
DOI: 10.3317/jraas.2000.005 -
British Journal of Pharmacology Nov 19931. The hyperalgesic activities in rats of bradykinin, carrageenin and lipopolysaccharide (LPS) were investigated in a model of mechanical hyperalgesia. 2. Bradykinin and...
1. The hyperalgesic activities in rats of bradykinin, carrageenin and lipopolysaccharide (LPS) were investigated in a model of mechanical hyperalgesia. 2. Bradykinin and carrageenin evoked dose-dependent hyperalgesia with maximum responses of similar magnitude to responses to LPS (1 and 5 micrograms). 3. Hoe 140, an antagonist of BK2 receptors, inhibited in a dose-dependent manner hyperalgesic responses to bradykinin, carrageenin and LPS (1 microgram) but not responses to LPS (5 micrograms), prostaglandin E2, dopamine, tumour necrosis factor alpha (TNF alpha), IL-1, IL-6 and IL-8. 4. Responses to bradykinin and LPS (1 and 5 micrograms) were inhibited by the cyclo-oxygenase inhibitor, indomethacin and by the beta-adrenoceptor antagonist, atenolol. The effects of indomethacin and atenolol were additive: their combination abolished responses to bradykinin and LPS (1 microgram) and markedly attenuated the response to LPS (5 micrograms). 5. Antiserum neutralizing endogenous TNF alpha abolished the response to bradykinin whereas antisera neutralizing endogenous IL-1 beta, IL-6 and IL-8 each partially inhibited the response. The combination of antisera neutralizing endogenous IL-1 beta+IL-8 or IL-6+IL-8 abolished the response to bradykinin. 6. Antisera neutralizing endogenous TNF alpha, IL-1 beta, IL-6 and IL-8 each partially inhibited responses to LPS (1 and 5 micrograms). Increasing the dose of antiserum to TNF alpha or giving a combination of antisera to IL-1 beta+IL-8 or IL-6+IL-8 further inhibited responses to LPS (1 and 5 micrograms). 7. These data show that bradykinin can initiate the cascade of cytokine release that mediates hyperalgesic responses to carrageenin and endotoxin (1 microgram). The lack of effect of Hoe 140 on hyperalgesic responses to LPS (5 microgram) suggests that the release of hyperalgesic cytokines can be initiated independently of bradykinin BK2 receptors.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Atenolol; Bradykinin; Carrageenan; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Hyperalgesia; Indomethacin; Inflammation; Lipopolysaccharides; Male; Rats; Rats, Wistar; Time Factors
PubMed: 8298813
DOI: 10.1111/j.1476-5381.1993.tb13946.x -
American Journal of Physiology. Heart... Jul 2001In the serum of 116 healthy individuals, exogenous bradykinin (BK) half-life (27 +/- 10 s) was lower than that of des-Arg(9)-BK (643 +/- 436 s) and was statistically... (Comparative Study)
Comparative Study
In the serum of 116 healthy individuals, exogenous bradykinin (BK) half-life (27 +/- 10 s) was lower than that of des-Arg(9)-BK (643 +/- 436 s) and was statistically different in men compared with women. The potentiating effect of an angiotensin-converting enzyme (ACE) inhibitor was, however, more extensive for BK (9.0-fold) than for des-Arg(9)-BK (2.2- fold). The activities of ACE, aminopeptidase P (APP), and kininase I were respectively 44 +/- 12, 22 +/- 9, and 62 +/- 10 nmol x min(-1) x ml(-1). A mathematical model (y = kt(alpha)e(-beta t), t > 0), applied to the BK kinetically released from endogenous high-molecular-weight kininogen (HK) during plasma activation in the presence of an ACE inhibitor, revealed a significant difference in the rate of formation of BK between men and women. For des-Arg(9)-BK, the active metabolite of BK, the rate of degradation was higher in women compared with men, correlating significantly with serum APP activity (r(2) = 0.6485, P < 0.001). In conclusion, these results constitute a basis for future pathophysiological studies of inflammatory processes where activation of the contact system of plasma and the kinins is involved.
Topics: Adult; Aged; Bradykinin; Female; Half-Life; Humans; Kinetics; Kinins; Lysine Carboxypeptidase; Male; Metalloendopeptidases; Middle Aged; Peptidyl-Dipeptidase A; Plasma
PubMed: 11406494
DOI: 10.1152/ajpheart.2001.281.1.H275 -
British Journal of Pharmacology Feb 2002
Review
Topics: Aminopeptidases; Angiotensin-Converting Enzyme Inhibitors; Animals; Apoptosis; Autocrine Communication; Bradykinin; Humans; Ischemic Preconditioning, Myocardial; Myocardial Ischemia; Myocardial Reperfusion Injury; Neprilysin; Paracrine Communication
PubMed: 11861312
DOI: 10.1038/sj.bjp.0704548